Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center

Abstract

The local recurrence rate of phyllodes tumors of the breast varies widely among different subtypes, and distant metastasis is associated with poor survival. This study aimed to identify factors that are predictive of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with phyllodes tumors of the breast. Clinical data of all patients with a phyllodes tumor of the breast (n = 192) treated at Sun Yat-sen University Cancer Center between March 1997 and December 2012 were reviewed. The Pearson Χ² test was used to investigate the relationship between clinical features of patients and histotypes of tumors. Univariate and multivariate Cox regression analyses were performed to identify factors that are predictive of LRFS, DMFS, and OS. In total, 31 (16.1%) patients developed local recurrence, and 12 (6.3%) developed distant metastasis. For the patients who developed local recurrence, the median age at the diagnosis of primary tumor was 33 years (range, 17-56 years), and the median size of primary tumor was 6.0 cm (range, 0.8-18 cm). For patients who developed distant metastasis, the median age at the diagnosis of primary tumor was 46 years (range, 24-68 years), and the median size of primary tumor was 5.0 cm (range, 0.8-18 cm). In univariate analysis, age, size, hemorrhage, and margin status were found to be predictive factors for LRFS (P = 0.009, 0.024, 0.004, and 0.001, respectively), whereas histotype, epithelial hyperplasia, margin status, and local recurrence were predictors of DMFS (P = 0.001, 0.007, 0.007, and < 0.001, respectively). In multivariate analysis, independent prognostic factors for LRFS included age [hazard ratio (HR) = 3.045, P = 0.005], tumor size (HR = 2.668, P = 0.013), histotype (HR = 1.715, P = 0.017), and margin status (HR = 4.530, P< 0.001). Histotype (DMFS: HR = 4.409, P = 0.002; OS: HR = 4.194, P = 0.003) and margin status (DMFS: HR = 2.581, P = 0.013; OS: HR = 2.507, P = 0.020) were independent predictors of both DMFS and OS. In this cohort, younger age, a larger tumor size, a higher tumor grade, and positive margins were associated with lower rates of LRFS. Histotype and margin status were found to be independent predictors of DMFS and OS.

Figure 1.. The inclusion diagram of patients with phyllodes tumors of the breast.

Eighteen patients were excluded because of the lack of pathologic slides or complete follow-up records, and 8 were excluded because of concurrent diagnosis of other malignancies. Local recurrence (LR) occurred in 31 patients, and distant metastasis (DM) occurred in 12 patients.

Figure 2.. The three subtypes of phyllodes tumors (HE ×100).

A, benign phyllodes tumor; B, borderline phyllodes tumor; C, malignant phyllodes tumor. According to the World Health Organization (WHO) classification criteria, benign tumors were identified when <5 mitoses/10 high-power fields (HPFs), pushing margins, minimal or moderate stromal overgrowth, and minimal stromal cellularity and atypia were observed; borderline phyllodes tumor were identified when 5-9 mitoses/10 HPFs, pushing or infiltrating margins, moderate stromal cellularity, atypia, and overgrowth were observed; and malignant phyllodes tumors were identified when >10 mitoses/10 HPFs, infiltrating margins, moderate to marked stromal cellularity, atypia, and overgrowth were observed.

Figure 3.. Overall survival (OS) curves of patients with phyllodes tumors stratified by histotype, margin, local recurrence, and distant metastasis.

A, patients with malignant phyllodes tumors had a higher OS rate than did patients with other subtypes of phyllodes tumors (P < 0.001). B, the presence of positive margins was a poor prognostic factor for OS (P < 0.001). C, patients who developed local recurrence had reduced survival compared with those who did not (P < 0.001). D, patients who developed distant metastasis also had reduced survival compared with those who did not (P < 0.001).